Debromination, spontaneous

The 1,3-dipolar cycloaddition of diazoalkanes 276 and nitrile oxides 279 to isothiazole dioxides 275 provides an easy entry into fused bicyclic isothiazole systems 277 and 280, respectively <06JHC1045>. The adducts from 4-bromoisothiazole (R1 = Br) are labile and undergo spontaneous debromination to form the aromatic bicyclic pyrazolo-isothiazoles 278... 

Swartz and Stenzel (1984) proposed an approach to widen the applicability of the cathode initiation of the nucleophilic substitution, by using a catalyst to facilitate one-electron transfer. Thus, in the presence of PhCN, the cathode-initiated reaction between PhBr and Bu4NSPh leads to diphe-nydisulfide in such a manner that the yield increases from 10 to 70%. Benzonitrile captures an electron and diffuses into the pool where it meets bromobenzene. The latter is converted into the anion-radical. The next reaction consists of the generation of the phenyl radical, with the elimination of the bromide ion. Since generation of the phenyl radical takes place far from the electrode, this radical is attacked with the anion of thiophenol faster than it is reduced to the phenyl anion. As a result, instead of debromination, substitution develops in its chain variant. In other words, the problem is to choose a catalyst such that it would be reduced more easily than a substrate. Of course, the catalyst anion-radical should not decay spontaneously in a solution. 

The bromination of dibenzoazepine 63 in 1,2-dichloroethane gives the /raw.v-dibromide 64 as the only product. The reaction was monitored spectrophotometrically and found to exhibit a third-order kinetics (second-order in Br2). A significant conductivity has also been found during the course of bromination. Both spectrophotometric and conductometric measurements are consistent with the presence of Br3- salt intermediates at a maximum concentration of ca 2% of that of the initial reactants. The X-ray structure of dibromide 64 shows a considerable strain at carbons bearing bromine atoms. The strain appears to be responsible for an easy, spontaneous debromination of 64, as well as for high barrier for the formation of 64 from the bromonium-tribromide intermediate. That makes possible the cumulation of the intermediate itself during the bromination of 63119. 

The second piece of evidence for the intermediacy of the dimeric peroxide, 32, stems from the low temperature ozonolysis of trans-2,3-dibromo-2-butene, 23. In contrast to the usual reactions which were carried out at ca. —35°C, the ozonolysis of 23 in pentane at —78°C yielded a solid white precipitate which exploded violently when we tried to isolate it. When the low temperature ozonolysis was carried out in methylene chloride, on the other hand, no precipitate appeared. However, when the methylene chloride solution of the ozonolysis product was allowed to warm up gradually, an exothermic reaction set in at around —50 °C, and the originally colorless solution showed the typical color of dissolved bromine. It is assumed that the explosive material is the dimeric peroxide, 32, which undergoes spontaneous debromination to form diacetyl peroxide, 33. 

On the basis of the results discussed above for the reaction of NBS with simple 3-substituted indoles, a 3-bromoindolenine appears to be the first initial intermediate, which, following path A or B, undergoes spontaneous debromination through a series of oxidation and hydrolysis reactions. These reactions lead to the formation of an oxindole derivative, which promotes the cleavage reaction. The third equiv. of NBS forms a stable 5-bromooxindole derivative. 

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